COQ7 pathogenetic variants cause primary CoQ(10) deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ(10) supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ(10) levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ(10) (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ(10) deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.

COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction / Pettenuzzo, Ilaria; Carli, Sara; Sánchez-Cuesta, Ana; Isidori, Federica; Montanari, Francesca; Grippa, Mina; Lanzoni, Giulia; Ambrosetti, Irene; Di Pisa, Veronica; Cordelli, Duccio Maria; Mondardini, Maria Cristina; Pippucci, Tommaso; Ragni, Luca; Cenacchi, Giovanna; Costa, Roberta; Lima, Mario; Capristo, Maria Antonietta; Tropeano, Concetta Valentina; Caporali, Leonardo; Carelli, Valerio; Brunelli, Elena; Maffei, Monica; Ahmed Sheikhmaye, Hodman; Fetta, Anna; Brea-Calvo, Gloria; Garone, Caterina. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - ELETTRONICO. - 1:(2024), pp. 1-9. [10.1038/s41431-024-01615-w]

COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction

Pettenuzzo, Ilaria;Carli, Sara;Isidori, Federica;Grippa, Mina;Lanzoni, Giulia;Ambrosetti, Irene;Di Pisa, Veronica;Cordelli, Duccio Maria;Pippucci, Tommaso;Ragni, Luca;Cenacchi, Giovanna;Costa, Roberta;Lima, Mario;Tropeano, Concetta Valentina;Caporali, Leonardo;Carelli, Valerio;Fetta, Anna;Garone, Caterina
2024

Abstract

COQ7 pathogenetic variants cause primary CoQ(10) deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ(10) supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ(10) levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ(10) (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ(10) deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.
2024
COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction / Pettenuzzo, Ilaria; Carli, Sara; Sánchez-Cuesta, Ana; Isidori, Federica; Montanari, Francesca; Grippa, Mina; Lanzoni, Giulia; Ambrosetti, Irene; Di Pisa, Veronica; Cordelli, Duccio Maria; Mondardini, Maria Cristina; Pippucci, Tommaso; Ragni, Luca; Cenacchi, Giovanna; Costa, Roberta; Lima, Mario; Capristo, Maria Antonietta; Tropeano, Concetta Valentina; Caporali, Leonardo; Carelli, Valerio; Brunelli, Elena; Maffei, Monica; Ahmed Sheikhmaye, Hodman; Fetta, Anna; Brea-Calvo, Gloria; Garone, Caterina. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - ELETTRONICO. - 1:(2024), pp. 1-9. [10.1038/s41431-024-01615-w]
Pettenuzzo, Ilaria; Carli, Sara; Sánchez-Cuesta, Ana; Isidori, Federica; Montanari, Francesca; Grippa, Mina; Lanzoni, Giulia; Ambrosetti, Irene; Di Pisa, Veronica; Cordelli, Duccio Maria; Mondardini, Maria Cristina; Pippucci, Tommaso; Ragni, Luca; Cenacchi, Giovanna; Costa, Roberta; Lima, Mario; Capristo, Maria Antonietta; Tropeano, Concetta Valentina; Caporali, Leonardo; Carelli, Valerio; Brunelli, Elena; Maffei, Monica; Ahmed Sheikhmaye, Hodman; Fetta, Anna; Brea-Calvo, Gloria; Garone, Caterina
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/969742
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